Sodium hydride → HCID 10413115, compound

HRID 1837355Notes

Reaction equation

HRID 1837355 reaction equation
[H-].[Na+].[S:3]1[CH:7]=[CH:6][CH:5]=[C:4]1[CH2:8][OH:9].[Cl:10][C:11]1[CH:16]=[C:15]([Cl:17])[C:14]([O:18][CH3:19])=[CH:13][C:12]=1[NH:20][C:21]1[C:30]2[C:25](=[CH:26][C:27](F)=[C:28]([O:31][CH3:32])[CH:29]=2)[N:24]=[CH:23][C:22]=1[C:34]#[N:35].C(=O)(O)[O-].[Na+]>CS(C)=O>[Cl:10][C:11]1[CH:16]=[C:15]([Cl:17])[C:14]([O:18][CH3:19])=[CH:13][C:12]=1[NH:20][C:21]1[C:30]2[C:25](=[CH:26][C:27]([O:9][CH2:8][C:4]3[S:3][CH:7]=[CH:6][CH:5]=3)=[C:28]([O:31][CH3:32])[CH:29]=2)[N:24]=[CH:23][C:22]=1[C:34]#[N:35]

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 694672-ThiophenemethanolHCID 516892Sodium BicarbonateHCID 114861534-[(2,4-Dichloro-5-methoxyphenyl)amino]-7-fluoro-6-methoxy-3-quinolinecarbonitrile

Product 1

HCID 10413115HCID 10413115, compoundYield 33%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a mixture of sodium hydride (37 mg, 1.54 mmol) in 3 mL of dimethylsulfoxide is added 2-thiophenemethanol (48 mg, 0.42 mmol). The solution is stirred at room temperature for 45 minutes. 4-[(2,4-Dichloro-5-methoxyphenyl)amino]-7-fluoro-6-methoxy-3-quinolinecarbonitrile (150 mg, 0.38 mmol) is added and the reaction mixture is heated at 100° C. overnight, then cooled to room temperature. The reaction mixture is poured into saturated sodium bicarbonate and the solids are collected by filtration. Purification by flash column chromatography eluting with 1:1 hexane:ethyl acetate provides 61 mg of 4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-7-(2-thienylmethoxy)-3-quinolinecarbonitrile, mp 194-196° C.

Workup

  1. temperaturethe reaction mixture is heated at 100° C. overnight
  2. temperaturecooled to room temperature
  3. filtrationthe solids are collected by filtration
  4. customPurification by flash column chromatography
  5. washeluting with 1:1 hexane

Sources & evidence

ORD record
ord-2bf1e777448d48fd9a1afa5ad95a9a73
Source dataset
uspto-grants-2004_08
Patent number
US06780996B2

Reaction notes

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